Delivery system for heparin-binding growth factors

a technology of growth factor and delivery system, which is applied in the field of proteoglycans, can solve the problems of defective endochondral ossification, large amount of inventive proteoglycan production, and severe disorganization of the columnar structure of chondrocytes

Inactive Publication Date: 2010-03-02
UNIVERSITY OF DELAWARE
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

Furthermore, large amounts of the inventive proteoglycan can be produced in mammalian cell lines.
Consistent with a fundamental role for Pln in endochondral bone formation, targeted disruption of the Pln gene in mice results in severe disorganization of the columnar structure of chondrocytes and defective endochondral ossification (9).
Although it is known that perlecan is involved in growth factor retention, the intact molecule is too large to exploit commercially as a growth factor adhesive.
Perlecan is one of the most complex gene products because of its enormous dimensions and number of posttranslational modifications.
Its size does not allow for efficient and cost effective commercial production.

Method used

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  • Delivery system for heparin-binding growth factors
  • Delivery system for heparin-binding growth factors
  • Delivery system for heparin-binding growth factors

Examples

Experimental program
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Effect test

example 1

Materials and Methods

Materials

[0042]Pln / HSPG2 was obtained from Becton-Dickinson Labware (Bedford, Mass.). The rabbit polyclonal antibody against rat aggrecan was provided by Dr. Kurt Doege (Shriner's Hospital for Children, Portland Unit). The rabbit anti-mouse antibody against type X collagen (PXNC1-88) was provided by Dr. Greg Lunstrum (Shriner's Childrens Hospital, Portland, Oreg.) The rabbit IgG antibody against mouse type II collagen was purchased from Biodesign International (catalog # T40025R). Species-specific, Texas-Red conjugated secondary antibodies were purchased from Amersham Corporation (Arlington Heights, Ill.).

Immunofluorescent Detection of Extracellular Matrix Components

[0043]After culture upon matrix for 6 or 9 days, cell aggregates and monolayers were rinsed twice with Dulbecco's phosphate buffered saline (D-PBS) without calcium or magnesium. The specimens were subsequently fixed, washed 3 times (5 minutes at room temperature) with D-PBS and incubated with the pri...

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Abstract

New uses of proteoglycans to bind and present growth factors, methods of accelerating wound, tissue or bone repair using such proteoglycans, pharmaceutical compositions of such proteoglycans, and scaffolds coated with such proteoglycans are disclosed. The proteoglycan of the invention is derived from domain I or perlecan.

Description

RELATED APPLICATIONS[0001]This application is a national stage application (under 35 U.S.C. 371) of PCT / US01 / 26512 filed Aug. 27, 2001, which claims the benefit of U.S. Application No. 60 / 228,935 filed Aug. 30, 2000, which is hereby incorporated herein in its entirety.GOVERNMENT INTERESTS[0002]This invention was made with Government support under Grant (or Contract) No. HD25235 awarded by the National Institutes of Health. The Government has certain rights in this invention.BACKGROUND OF THE INVENTION[0003]The invention provides new uses and compositions of proteoglycans. The proteoglycans are derived from perlecan, an extracellular matrix protein. The inventive proteoglycans retain certain desirable activities of the full-length perlecan molecule, such as the ability to bind growth factors, yet they have a size that allows for effective preparation and application as is not the case for perlecan. Furthermore, large amounts of the inventive proteoglycan can be produced in mammalian ...

Claims

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Application Information

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Patent Type & Authority Patents(United States)
IPC IPC(8): A61K38/17A61K38/18A61L27/40C07K14/47C07K14/475A61K38/39A61L27/54
CPCA61K38/1709A61K38/39A61L27/54A61L27/36A61L27/22A61L2300/236A61L2300/252A61L2300/414A61P17/02A61P19/00A61P19/04
Inventor CARSON, DANIEL D.FARACH-CARSON, MARY C.FRENCH, MARGARETGOMES, RONALDTIMPL, RUPERT
Owner UNIVERSITY OF DELAWARE
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